Variant 3-183978614-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005688.4(ABCC5):c.1185T>C(p.Ala395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,613,508 control chromosomes in the GnomAD database, including 264,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 29078 hom., cov: 32)

Exomes 𝑓: 0.56 ( 235147 hom. )

Consequence

ABCC5
NM_005688.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Variant links:

Genes affected

ABCC5 (HGNC:56): (ATP binding cassette subfamily C member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ABCC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC5	NM_005688.4 linkuse as main transcript	c.1185T>C	p.Ala395=	synonymous_variant	9/30	ENST00000334444.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC5	ENST00000334444.11 linkuse as main transcript	c.1185T>C	p.Ala395=	synonymous_variant	9/30	1	NM_005688.4	P1	O15440-1
ABCC5	ENST00000265586.10 linkuse as main transcript	c.1185T>C	p.Ala395=	synonymous_variant	9/29	5			O15440-5
ABCC5	ENST00000492216.1 linkuse as main transcript	n.736T>C		non_coding_transcript_exon_variant	5/6	5
ABCC5	ENST00000437205.5 linkuse as main transcript	c.1185T>C	p.Ala395=	synonymous_variant, NMD_transcript_variant	9/30	5

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92855

AN:

151868

Hom.:

29048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.725

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.578

AC:

144055

AN:

249052

Hom.:

42868

AF XY:

0.573

AC XY:

77409

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.740

Gnomad AMR exome

AF:

0.522

Gnomad ASJ exome

AF:

0.550

Gnomad EAS exome

AF:

0.851

Gnomad SAS exome

AF:

0.547

Gnomad FIN exome

AF:

0.502

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.564

AC:

824033

AN:

1461522

Hom.:

235147

Cov.:

AF XY:

0.563

AC XY:

409141

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.528

Gnomad4 ASJ exome

AF:

0.552

Gnomad4 EAS exome

AF:

0.853

Gnomad4 SAS exome

AF:

0.541

Gnomad4 FIN exome

AF:

0.510

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.611

AC:

92935

AN:

151986

Hom.:

29078

Cov.:

AF XY:

0.606

AC XY:

45023

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.725

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.853

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.626

Alfa

AF:

0.569

Hom.:

55127

Bravo

AF:

0.622

Asia WGS

AF:

0.707

AC:

2459

AN:

3478

EpiCase

AF:

0.564

EpiControl

AF:

0.577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.13

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over